Research topics

The research conducted in our laboratory focuses on studying the epigenetic mechanisms that play a role in regulating genes associated with the differentiation of Th17 cells. Th17 cells are a specific subset of T helper lymphocytes that produce interleukins 17A and 17F. These cells have been implicated in initiating detrimental immune responses that lead to tissue destruction in autoimmune diseases. Our research aims to unravel the precise molecular mechanisms underlying the epigenetic changes during Th17 cell differentiation. By gaining a deeper understanding of these mechanisms, we anticipate that we can eventually intervene directly in these processes. For instance, we hope to modulate the negative impact of Th17 lymphocytes in autoimmune diseases by targeting the specific epigenetic changes involved.
Another research topic we are interested in our laboratory is the role of sirtuins in multidrug resistance of melanomas. Late diagnosis of melanoma is associated with a median life of 2-8 months and only 10% of patients survive 5 years from diagnosis. Drug resistance is the phenomenon of cancer cells acquiring resistance to chemotherapeutic agents and is the main reason for the ineffectiveness of chemotherapy. A cancerous tumor is a mixture of several cell populations with different sensitivities to drugs.

Chemotherapy kills only those cells that are sensitive to it, thus it can lead to an enrichment of the titer of resistant cells. If the tumor starts to grow again, subsequent chemotherapy (also with a drug from a different class) may be ineffective, because most of the tumor cells will be a highly resistant population. Malignant melanoma is intrinsically resistant to many types of therapy, including radiotherapy or conventional chemotherapy. Our results show that sirtuins (enzymes with the activity of mono-ADP-ribosyltransferases or deacetylases) may play a key role in the regulation of genes related to the acquisition of drug resistance by melanoma cells in the vertical growth phase.
The RORC gene (located on 1q21) gives rise to two human isoforms, RORγ and RORγT, through the utilization of two distinct promoters. The expression of the RORγT receptor is limited to certain subsets of activated T cells and is crucial for initiating the differentiation of naive CD4+ T cells into Th17 cells. Th17 lymphocytes have been implicated in promoting the development of various autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, psoriasis, Crohn’s disease, and type I diabetes.

Apart from their role in immune regulation, RORγ and RORγT also participate in lipid metabolism and the regulation of the circadian cycle. In our research, we are actively seeking agonists or inverse agonists for these two receptors. The objective is to identify substances that can be utilized in adoptive cell therapy, specifically targeting cancer cells, or substances that can inhibit the activity of Th17 cells in the context of autoimmune diseases. By modulating the activity of these receptors, we aim to develop potential therapeutic interventions for cancer treatment and the management of autoimmune conditions.